Utility of Leflunomide in the Treatment of Complex Cytomegalovirus Syndromes

Avery, Robin K.; Mossad, Sherif B.; Poggio, Emilio D.; Lard, Michelle; Budev, Marie; Bolwell, Brian J.; Waldman, W. James; Braun, W; Mawhorter, Steven D.; Fatica, Richard; Krishnamurthi, Venkatesh; Young, James; Shrestha, Rabin K.; Stephany, Brian; Lurain, Nell S.; Yen‐Lieberman, Belinda

doi:10.1097/tp.0b013e3181e94106

Cited by 111 publications

(89 citation statements)

References 33 publications

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“…As ganciclovir, foscarnet and cidofovir act at the level of the viral DNA polymerase, cross resistance may occur. Case reports describe multidrug AIC246 Multidrug-Resistant CMV Disease resistance in SOT recipients, and in these cases unproven or experimental therapies are necessarily employed (8,15). Leflunomide, an immunomodulatory agent used in the treatment of rheumatic diseases, has been reported to successfully treat patients intolerant of or resistant to conventional agents (15).…”

Section: Discussionmentioning

confidence: 99%

First Report of Successful Treatment of Multidrug-Resistant Cytomegalovirus Disease with the Novel Anti-CMV Compound AIC246

Kaul

Stoelben

Cober

et al. 2011

American Journal of Transplantation

156

111

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We report the first case of cytomegalovirus (CMV) disease treated with AIC246, a novel anti-CMV compound which targets the viral terminase complex and remains active against virus resistant to DNA polymerase inhibitors. A lung transplant recipient developed refractory multidrug-resistant CMV disease involving the lungs, gastrointestinal tract and retina. His disease progressed despite treatment with all DNA polymerase inhibitors; multiple agents reported to have activity against CMV in case series, and reduction in his immunosuppressive medications. AIC246 which is in clinical development was obtained for emergency use, and combined with additional reduction in immunosuppression resulted in rapid clinical, virological and radiological resolution of disease. The patient has remained free of CMV disease or viremia off treatment for greater than 3 months. In summary AIC246, while still in development, may be a promising alternative to current therapies.

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Section: Discussionmentioning

confidence: 99%

First Report of Successful Treatment of Multidrug-Resistant Cytomegalovirus Disease with the Novel Anti-CMV Compound AIC246

Kaul

Stoelben

Cober

et al. 2011

American Journal of Transplantation

156

111

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show abstract

“…Its side effects includes gastrointestinal toxicity with diarrhea, liver toxicity and polyneuropathy. Given the relatively slow onset of complete antiviral action, the drug is not however ideal for infections with rapidly increasing viral loads [53]. Its proper dosage, timing and duration of treatment for CMV need further investigations in future randomized studies [54].…”

Section: Antiviral Drug Resistancementioning

confidence: 99%

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Madon

Giaccone

Festuccia

et al. 2016

Expert Review of Hematology

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“…Patients suspected to have infection due to drug-resistant virus should have viral genotype analysis to detect mutations in UL97 and UL54 to define the phenotype of ganciclovir resistance or possible cross-resistance to other antiviral drugs (foscarnet and cidofovir) (209)(210)(211). Laboratory testing for drug-resistant CMV was recently reviewed in this journal (209).…”

Section: Relapse and Resistancementioning

confidence: 99%

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

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Utility of Leflunomide in the Treatment of Complex Cytomegalovirus Syndromes

Abstract: Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.

Cited by 111 publications

References 33 publications

First Report of Successful Treatment of Multidrug-Resistant Cytomegalovirus Disease with the Novel Anti-CMV Compound AIC246

First Report of Successful Treatment of Multidrug-Resistant Cytomegalovirus Disease with the Novel Anti-CMV Compound AIC246

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

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